We have observed, in previous GCRC-supported studies of patients with chronic renal failure, that progression in negatively correlated with serum level of DHEA-S; i.e., patients with relatively low levels of this hormone (for their age and gender) progress rapidly while patients with relatively high levels progress slowly. Based on this finding, we have instituted a double-blind, randomized, crossover, dose- adjustment trial of DHEA supplementation in patients with chronic renal failure. After establishing (by sequential determinations of glomerular filtration rate) (GFR) that progression is occurring, we randomize patients to receive either placebo or DHEA first, followed by the opposite, in two equal periods of observation, varying in length from 2 to 6 months (depending on the prior rate of progression). Serum levels of DHEA-S are measured weekly for the first four weeks of both periods, and reported to an unblinded individual, who adjusts the dosage of DHEA capsules vs. placebo capsules so as to achieve a serum DHEA-S level approximating 12 ug/ml (in those receiving DHEA). So far 8 patients have entered this protocol. Two patients, one with non- insulin-dependent diabetes mellitus and one with IgA nephropathy, have shown accelerated progression during DHEA supplementation. One patient with insulin-dependent diabetes mellitus and one with polycystic kidney disease have shown slowed progression during DHEA supplementation. Our future studies will be limited to these latter two disorders. DHEA toxicity has not been noted otherwise.